The California Teachers Study (CTS) is a prospective study of 133,479 California teachers initiated in 1995 by a consortium of California research centers with expertise in epidemiology and cancer etiology. The study was designed to understand better the etiology and prevention of breast cancer and of other major women's health problems; as such, the initiation of the cohort was supported by California tobacco taxes targeted to breast cancer research. Members of the cohort were identified through their participation in the California State Teachers Retirement System (STRS) to which all public school teachers and administrators must belong. An early observation from the CTS cohort is the extraordinarily high breast cancer rates experienced by California teachers. Incidence rates for invasive breast cancer are approximately 51% higher than those expected among women of comparable age and race in California. Moreover we have reported that the CTS cohort has very high rates of endometrial and ovarian cancers as well as melanoma. Among the strengths of the CTS cohort are its size and the detailed exposure and lifestyle assessment made at baseline and through subsequent contacts with cohort members. We were able to gather more detailed data from participants in the CTS than are typically collected from members of other large healthy cohorts, primarily because of the uniformly high education levels of the CTS membership. The scientific specific aims for the next five years of the CTS are focused around a small series of detailed exposure characteristics, including various patterns of hormone therapy (HT) use, dietary intake of isothiocyanates, alcohol consumption, and physical activity/energy balance. Because of the size and excellent follow-up of the CTS, we will expand the cancer outcomes of interest for selected hypotheses to include not just breast cancer as in the previous funding period, but also colorectal cancer, endometrial cancer, ovarian cancer, and lung cancer. We also propose to target 2,500 incident breast cancer patients and an equal sample of healthy CTS participants for blood collection and DNA extraction to evaluate a series of hypotheses regarding genetically-based modification of or interactions with certain exposure/breast cancer relationships. Finally, we propose to maintain the sophisticated infrastructure already in place, to continue detailed follow-up and periodic recontact of CTS members, and to process new data and continue analysis of existing data on CTS participants.